Combinations of type 1 diabetes, celiac disease and allergy : An immunological challenge

Abstract: The immune system is composed of a complex network of different cell types protecting the body against various possible threats. Among these cells are T-helper (Th) cells type 1 (Th1) and type 2 (Th2), as well as T regulatory (Treg) cells. Th1 and Th2 are supposed to be in balance with each other, while Tregs regulate the immune response, by halting it when the desired effect, i.e. destroying the threat, is acquired. However, sometimes this intricate interplay in the immune system is disturbed, leading to diseases as type 1 diabetes (T1D), celiac disease or allergic disease. According to the paradigm claiming that Th1- and Th2-cells inhibit each other a coexistence of a Th1-deviated disease and a Th2-deviated disease seems unlikely.This thesis aimed to examine the immune response with focus on subsets of T-cells in children with T1D, celiac disease, allergy, or a combination of two of these diseases, in comparison to reference children (healthy).In line with previous findings we observed that children with celiac disease showed a decreased spontaneous Th2-associated secretion, whereas children with allergic disease showed increased birch- and cat-induced Th2-associated response.The most remarkable results in this thesis are those observed in children with combinations of diseases. The combination of T1D and celiac disease decreased the Th1-associated response against several antigens, but instead displayed a more pronounced Treg-associated response. Further, in children with combined T1D and allergy an increased Th1- and Th2-associated response was seen to a general stimulus, and an increased birch-induced Th1-, Th2-, Treg- and pro-inflammatory response. In contrast, the combination of allergy and celiac disease showed a decreased spontaneous Th1-, Th2-, Treg- and pro-inflammatory response.In conclusion, we observed that two Th1-deviated diseases in combination suppress the immune response and increase the regulatory activity. Further it seems that allergy has the ability to shift the immune response in diverging directions depending on which disease it is combined with. The observed suppressive effect might be due to exhaustion of the immune system from the massive pressure of two immunological diseases in combination, while the pronounced Treg response might be caused by an attempt to compensate for the dysfunction. These results shed some light on the intriguing and challenging network that constitutes the immune system, and hopefully give clues regarding disease prevention and treatment.